Leronlimab in Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation

A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation

Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in coronavirus disease 2019 (COVID-19).

The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).

Study Overview

• Status: Suspended
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Placebo; Drug: Leronlimab

Detailed Description

Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). CCR5 is expressed predominantly on T cells but also found on macrophages, dendritic cells, and eosinophils to mediate chemotaxis in response to its cognate ligands that include CCL5 (RANTES), CCL3 (MIP-1α), and CCL4 (MIP-1β). These ligands are integral in the recruitment of these immune cells to inflammatory sites. The immunopathogenesis of COVID-19 likely involves the excessive influx of immune cells into the lung. Disruption of the CCL5-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in COVID-19.

The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).

This is a Phase 3, 2-arm, randomized, double blind, placebo controlled, multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) as an add on therapy to the institutional standard of care (SoC) for the management of critically ill patients with COVID-19 pneumonia.

Patients will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab (PRO 140) or placebo. Leronlimab or placebo will be administered by 30-minute intravenous (IV) infusion weekly over a 4-week treatment period. No treatments will be administered post-discharge.

The participant will be evaluated on each study day while hospitalized up until and including Day 28. The daily visits will capture clinical status - ordinal scale and the occurrence of adverse events. A complete follow-up assessment will be performed at Days 7, 14, 21, 28, 42 and 60 for those who are hospitalized at these specific timepoints. Follow-up visits can be conducted as telephone or video contact visits, if subject is discharged from the hospital prior to the complete follow-up visits.

• Study Type: Interventional
• Enrollment (Anticipated): 316
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil
    • Hospital Israelita Albert Einstein
  • São Paulo, Brazil
    • Hospital M'Boi Mirim
  • BA
    • Ipiaú, BA, Brazil
      • Clinica São Roque
    • Salvador, BA, Brazil
      • Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
  • DF
    • Brasilia, DF, Brazil
      • Hospital do Coração do Brasil
  • ES
    • Laranjeiras, ES, Brazil
      • Hospital Dr Jayme dos Santos Neves
  • MG
    • Passos, MG, Brazil
      • Santa Casa de Misericórdia de Passos
  • Please Select
    • Sao Paulo, Please Select, Brazil
      • Hospital 9 De Julho
  • RJ
    • Rio De Janeiro, RJ, Brazil
      • Hospital São Lucas Copacabana
  • RN
    • Natal, RN, Brazil
      • Instituto Atena de Pesquisa Clínica
  • RS
    • Passo Fundo, RS, Brazil
      • Hospital São Vicente de Paulo
    • Porto Alegre, RS, Brazil
      • Hospital Mae de Deus
    • Porto Alegre, RS, Brazil
      • Irmandade da Santa Casa de Misericórdia Porto Alegre
  • SE
    • Aracaju, SE, Brazil
      • Centro de Pesquisa Clinica do Coracao
  • SP
    • Barretos, SP, Brazil
      • Fundação PIO XII
    • Bragança Paulista, SP, Brazil
      • Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista
    • Campinas, SP, Brazil
      • Instituto de Pesquisa Clínica de Campinas
    • Indaiatuba, SP, Brazil
      • Hospital Santa Ignes
    • Sao Paulo, SP, Brazil
      • Hospital Alemão Oswaldo Cruz
    • Sao Paulo, SP, Brazil
      • Hospital Beneficência Portuguesa
    • São José Do Rio Preto, SP, Brazil
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
    • São Paulo, SP, Brazil
      • BP Mirante
    • Votuporanga, SP, Brazil
      • Santa Casa de Votuporanga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or females aged ≥ 18 years
2. Critically ill patients with COVID-19 (defined as Ordinal Scale score of 7): Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for less than 72 hours.
3. Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.
4. Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).
5. Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.
6. Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.

Exclusion Criteria:

1. Subjects who had been on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for >72 hours prior to the screening.
2. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
3. Inability to provide informed consent (from subject or legally authorized representative) or to comply with test requirements.
4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.
5. Pregnancy or breast feeding.
6. Subject participating in another study with for an investigational treatment.
7. Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19), that may increase the risk for the study participant based on investigator judgement.
8. Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine).
9. Patients with estimated discharge or transfer for other hospital in the first 72 hours of study inclusion.
10. Patients with low probability of survival in the first 48 hours of study inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leronlimab (700 mg); Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge	Drug: Leronlimab; Leronlimab 700 mg
Placebo Comparator: Placebo; Placebo intravenously once a week (up to 4 doses) until hospital discharge	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative proportion of clinical recovery	Patients will be considered to have recovered if they attain categories 1, 2, or 3 on the eight-category ordinal scale within 28 days, as follows: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities and/or requiring home oxygen; Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients clinically recovered	Ordinal Scale of 1, 2 or 3	At days 14, 28, 42, and 60
All-cause mortality	All-cause mortality	At days 14, 28, 42, and 60
Proportion of patients discharged alive	Ordinal Scale 1 or 2	At days 14, 28, 42, and 60
Clinical Status	Ordinal Scale	Days 14, 28, 42, and 60
Duration of invasive mechanical ventilation or ECMO	Days	28 days
Length of hospital stay	Days	28 days
Length of ICU stay	Days	28 days

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: CytoDyn, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2021
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Pneumonia; COVID-19; Leronlimab
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Leronlimab
• Other Study ID Numbers: ARO_21_018_002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No